Atrial Fibrillation or Pulmonary EmbolismPhase 4NCT02066662
Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification
A Phase 4 study testing Rivaroxaban or Marcumar in people with Atrial Fibrillation or Pulmonary Embolism and Need of Long Term Oral Anticoagulation Therapy (OAT), run by RWTH Aachen University at 3 sites in Germany.
Trial summary
The following trial hypothesis will be proved: In patients with atrial fibrillation and/ or pulmonary embolism standard anticoagulant treatment with coumadin/phenprocoumon is associated with accelerated coronary or valvular calcification as assessed by cardiac computed tomography compared to the new anticoagulant… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation or Pulmonary Embolism, Need of Long Term Oral Anticoagulation Therapy (OAT), Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location
- What is being tested?
- Rivaroxaban or Marcumar
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 3 sitesGermany
- Study dates
- Jul 2013to Mar 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patient aged > 18 years
- Need for long-term OAT according to current international guidelines for the treatment of atrial fibrillation (ACC/(American Heart Association [AHA]/ European Society of Cardiology [ESC]guidelines) and / or pulmonary embolism (ACCP/ESC guidelines).
- Existent Coronary or Valvular Calcification, or both and an Agatston Score > 50 in at least one location as assessed by MSCT at Screening
- The anticipated minimum life expectancy is18 months
Who cannot join
- Patient has any clinical condition which does not allow initiation of long-term OAT including all contraindications such as hypersensitivity to active ingredient or other excipients, clinically relevant acute bleedings and all other risk circumstances according to Summary of Medicinal Product (SmPC) in which all warnings and preventive measures and precautions are described and have to be kept.
- Hypersensitivity to active substances investigated or to any of the excipients
- Patients had a previous coronary stent implantation in a way which makes coronary artery calcification scoring impossible or unreliable and no Valvular Calcification with Agatston Score > 50
- Chronic kidney disease (CKD) Stage V (GFR <15 mL)
- Liver disease with coagulopathy or other bleeding disorders including cirrhotic patients with Child Pugh B and C
- Acute gastrointestinal diseases
Show all 19Show fewer
- Clinically significant active bleeding
- Alcohol, opioids or drug abuse
- Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
- Patient is unwilling or unable to give informed consent
- Patient is unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
- Participation in a parallel interventional clinical trial
- Patient has been committed to an institution by legal or regulatory order
- Pregnant or lactating women
- Female patient capable of bearing children without highly effective methods of birth control
- Patient receives concomitant treatment with strong concurrent Cytochrome P 450 3A4 (CYP3A4)- and P- glycoprotein (P-gp)- inhibitors, i.e. azole-antimycotics (ketoconazole, itraconazole) or human immunodeficiency virus (HIV) protease inhibitors
- Neuraxial Anaesthesia or spinal/epidural puncture
- Known Endocarditis
- Known Lactose intolerance
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
University Hospital Aachen, Department of Cardiology
Aachen, North Rhine-Westphalia, 52074
Hospital Coburg, Med. Clinic II for Internal Medicine and Cardiology
Coburg, Bavaria, 96450
St.-Antonius-Hospital Eschweiler, Internal Medicine
Eschweiler, North Rhine-Westphalia, 52249
About this study
Official title: Influence of Rivaroxaban Compared to Vitamin K Antagonist Treatment Upon Development of Cardiovascular Calcification in Patients With Atrial Fibrillation and/ or Pulmonary Embolism (IRIVASC- Trial)
The following trial hypothesis will be proved: In patients with atrial fibrillation and/ or pulmonary embolism standard anticoagulant treatment with coumadin/phenprocoumon is associated with accelerated coronary or valvular calcification as assessed by cardiac computed tomography compared to the new anticoagulant therapy with rivaroxaban.
Read the detailed description
A multi center, prospective, controlled, open, randomized, interventional clinical trial blinded concerning outcome measurements with a two- arm parallel group design will be performed to investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed tomography scanning (MSCT) within one year follow-up.
In total 190 patients (95 patients per treatment arm) with atrial fibrillation and/ or pulmonary embolism with the indication for oral anticoagulation therapy will be enrolled.
After screening first cardiac CT scan will be performed in order to validate if calcium score is >50 which is an inclusion criteria. If the patient matches all other inclusion/exclusion criteria the remaining imaging procedures (Echocardiography, Intima Media Thickness of carotid artery (IMT) and Flow Mediated Vasodilatation (FMD), Electrocardiography (ECG) and blood pressure are executed. Pregnancy strip test will be executed and also serum chemistry, hematology, coagulation and batch analysis will be performed.
Patients will then be randomized to one of the two arms (Rivaroxaban or Marcumar) and will undergo the same examinations and measurements as described above at 1 week, 1, 6, 9 and 12 month Follow- Up (FU). In case of a positive result in respect to the primary endpoint a FU after 2 years will be performed.
Primary outcome measures will be assessed after all active patients will have completed 12-months study visit (interim analysis)
- Conditions
- Atrial Fibrillation or Pulmonary Embolism, Need of Long Term Oral Anticoagulation Therapy (OAT), Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location
- Being tested
- Rivaroxaban or Marcumar
- Keywords
- Coronary or Valvular Calcification, Agatston Score, Rivaroxaban, Coumarin, Oral Anticoagulation Therapy (OAT), Atrial Fibrillation, Pulmonary Embolism
- Medical subject headings
- Atrial Fibrillation, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban or MarcumarDrug
Also called Xarelto; Marcumar
Arm A: Rivaroxaban (tablet) for patients with atrial fibrillation: with 20 mg once daily for patients with eGFR > 49 ml per minute and 15 mg rivaroxaban once daily for patients with eGFR of 15 to 49 ml. Rivaroxaban (tablet) for patients with pulmonary embolism : 2x a day 15 mg at day 1-21 and 1x 20 mg from day 22 ongoing;
Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0.
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban | Experimental | Arm A: Rivaroxaban (tablet) for patients with atrial fibrillation: with 20 mg once daily for patients with eGFR > 49 ml per minute and 15 mg rivaroxaban once daily for patients with eGFR of 15 to 49 ml. Rivaroxaban (tablet) for patients with pulmonary embolism : 2x a day 15 mg at day 1-21 and 1x 20 mg from day 22 ongoing Receives: Drug: Rivaroxaban or Marcumar |
| Marcumar | Active comparator | Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0. Receives: Drug: Rivaroxaban or Marcumar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT)
To investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed. tomography scanning (MSCT) within one year follow-up
Measured: Cardiac Computertomography (CT) will be performed at screening, after 12 months and at 24 months
Secondary outcomes (4)
Serum chemistry including Matrix Gla Protein (MPG) level changes and Fetuin-A (baseline/ follow up)
Measured: baseline and 12 month Follow Up
Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD)
Measured: Baseline, 6, 12 and 24 month FU
Progression of aortic calcification (aortic Agatston Score)
Measured: screening and 12 month FU
Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging)
Measured: baseline, 6, 9, 12 and 24 month FU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startJul 2013
- Primary completionMar 2020
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial Fibrillation or Pulmonary EmbolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02066662
- Sponsor's protocol ID
- 12-001
- Status last verified
- Oct 2020
- First submitted
- 17 Feb 2014
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Rivaroxaban Compared to Vitamin K Antagonist Treatment Upon Development of Cardiovascular Calcification in Patients With Atrial Fibrillation and/ or Pulmonary Embolism (IRIVASC- Trial)
- ClinicalTrials.gov ID
- NCT02066662
- Acronym / sponsor ID
- 12-001
- Conditions
- Atrial Fibrillation or Pulmonary Embolism, Need of Long Term Oral Anticoagulation Therapy (OAT), Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location
- Keywords
- Coronary or Valvular Calcification, Agatston Score, Rivaroxaban, Coumarin, Oral Anticoagulation Therapy (OAT), Atrial Fibrillation, Pulmonary Embolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jul 2013
- Primary completion
- Mar 2020 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The following trial hypothesis will be proved: In patients with atrial fibrillation and/ or pulmonary embolism standard anticoagulant treatment with coumadin/phenprocoumon is associated with accelerated coronary or valvular calcification as assessed by cardiac computed tomography compared to the new anticoagulant therapy with rivaroxaban.
Detailed description
A multi center, prospective, controlled, open, randomized, interventional clinical trial blinded concerning outcome measurements with a two- arm parallel group design will be performed to investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed tomography scanning (MSCT) within one year follow-up.
In total 190 patients (95 patients per treatment arm) with atrial fibrillation and/ or pulmonary embolism with the indication for oral anticoagulation therapy will be enrolled.
After screening first cardiac CT scan will be performed in order to validate if calcium score is >50 which is an inclusion criteria. If the patient matches all other inclusion/exclusion criteria the remaining imaging procedures (Echocardiography, Intima Media Thickness of carotid artery (IMT) and Flow Mediated Vasodilatation (FMD), Electrocardiography (ECG) and blood pressure are executed. Pregnancy strip test will be executed and also serum chemistry, hematology, coagulation and batch analysis will be performed.
Patients will then be randomized to one of the two arms (Rivaroxaban or Marcumar) and will undergo the same examinations and measurements as described above at 1 week, 1, 6, 9 and 12 month Follow- Up (FU). In case of a positive result in respect to the primary endpoint a FU after 2 years will be performed.
Primary outcome measures will be assessed after all active patients will have completed 12-months study visit (interim analysis)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban | Experimental | Drug: Rivaroxaban or MarcumarArm A: Rivaroxaban (tablet) for patients with atrial fibrillation: with 20 mg once daily for patients with eGFR > 49 ml per minute and 15 mg rivaroxaban once daily for patients with eGFR of 15 to 49 ml. Rivaroxaban (tablet) for patients with pulmonary embolism : 2x a day 15 mg at day 1-21 and 1x 20 mg from day 22 ongoing |
| Marcumar | Active comparator | Drug: Rivaroxaban or MarcumarArm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patient aged > 18 years
- Need for long-term OAT according to current international guidelines for the treatment of atrial fibrillation (ACC/(American Heart Association [AHA]/ European Society of Cardiology [ESC]guidelines) and / or pulmonary embolism (ACCP/ESC guidelines).
- Existent Coronary or Valvular Calcification, or both and an Agatston Score > 50 in at least one location as assessed by MSCT at Screening
- The anticipated minimum life expectancy is18 months
Key exclusion criteria (19 listed)
- Patient has any clinical condition which does not allow initiation of long-term OAT including all contraindications such as hypersensitivity to active ingredient or other excipients, clinically relevant acute bleedings and all other risk circumstances according to Summary of Medicinal Product (SmPC) in which all warnings and preventive measures and precautions are described and have to be kept.
- Hypersensitivity to active substances investigated or to any of the excipients
- Patients had a previous coronary stent implantation in a way which makes coronary artery calcification scoring impossible or unreliable and no Valvular Calcification with Agatston Score > 50
- Chronic kidney disease (CKD) Stage V (GFR <15 mL)
- Liver disease with coagulopathy or other bleeding disorders including cirrhotic patients with Child Pugh B and C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban or MarcumarAlso: Xarelto; MarcumarArm A: Rivaroxaban (tablet) for patients with atrial fibrillation: with 20 mg once daily for patients with eGFR > 49 ml per minute and 15 mg rivaroxaban once daily for patients with eGFR of 15 to 49 ml. Rivaroxaban (tablet) for patients with pulmonary embolism : 2x a day 15 mg at day 1-21 and 1x 20 mg from day 22 ongoing; Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0. | Drug | Marcumar, Rivaroxaban |
Primary outcome
Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT)
Time frame: Cardiac Computertomography (CT) will be performed at screening, after 12 months and at 24 months
To investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed. tomography scanning (MSCT) within one year follow-up
4 secondary outcomes
Serum chemistry including Matrix Gla Protein (MPG) level changes and Fetuin-A (baseline/ follow up)
Time frame: baseline and 12 month Follow Up
Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD)
Time frame: Baseline, 6, 12 and 24 month FU
Progression of aortic calcification (aortic Agatston Score)
Time frame: screening and 12 month FU
Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging)
Time frame: baseline, 6, 9, 12 and 24 month FU
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rivaroxaban or Marcumar in people with Atrial Fibrillation or Pulmonary Embolism and Need of Long Term Oral Anticoagulation Therapy (OAT), run by RWTH Aachen University at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT) (time frame: Cardiac Computertomography (CT) will be performed at screening, after 12 months and at 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.